crossing96/oncoscreening huggingface dataset:
Prospective implementation of a nonopioid protocol for patients undergoing robot-assisted radical cystectomy with extracorporeal urinary diversion.	OBJECTIVES: To evaluate the feasibility and outcomes of a nonopioid (NOP) perioperative pain management protocol for patients undergoing robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: We prospectively included 52 consecutive patients undergoing RARC at our institution for bladder cancer. Patients received a multimodal pain management protocol, including a combination of nonopioid pain medications and regional anesthesia. For comparison, we retrospectively included 41 consecutive patients who received the same procedure before implementation of the NOP protocol. RESULTS: There was no significant difference in demographic and perioperative characteristics between the two groups. Patients included in the NOP protocol received a much lower dose of postoperative morphine milligram equivalents (2.5 [IQR: 0-23] vs. 44 [14.5-128], P < 0.001), with no difference in pain scores. In the NOP protocol, the median time to regular diet was significantly shorter (4days [IQR: 3-5] vs. 5days [IQR: 4-8], P = 0.002) and the length of stay was 2days shorter compared to the control group (5days [IQR: 4-7] vs. 7days [IQR: 6-11], P < 0.001). When evaluating the direct costs within 30days after initial surgery, the NOP protocol was associated with an 8.6% reduction as compared to the control group (P = 0.032). In multivariate analysis, the receipt of the NOP protocol was a significant predictor of a length of stay <7days after RARC (OR: 12.09; 95% CI: 1.70-140; P = 0.023). CONCLUSIONS: The prospective implementation of a NOP protocol for patients undergoing RARC is feasible, allowing for minimal narcotic usage and provides benefits to patients, institutions, and population.	bladder
Epidermal Growth Factor Receptor-Targeted Multifunctional Photosensitizers for Bladder Cancer Imaging and Photodynamic Therapy.	The in vitro and in vivo anticancer activity of iodinated photosensitizers (PSs) with and without an erlotinib moiety was investigated in UMUC3 [epidermal growth factor (EGFR)-positive] and T24 (EGFR-low) cell lines and tumored mice. Both the erlotinib-conjugated PSs 3 and 5 showed EGFR target specificity, but the position-3 erlotinib-PS conjugate 3 demonstrated lower photodynamic therapy efficacy than the corresponding non-erlotinib analogue 1, whereas the conjugate 5 containing an erlotinib moiety at position-17 of the PS showed higher tumor uptake and long-term tumor cure (severe combined immunodeficient mice bearing UMUC3 tumors). PS-erlotinib conjugates in the absence of light were ineffective in vitro and in vivo, but robust apoptotic and necrotic cell death was observed in bladder cancer cells after exposing them to a laser light at 665 nm. In contrast to (18)F-fluorodeoxyglucose, a positron emission tomography agent, the position-17 erlotinib conjugate ((124)I-analogue 6) showed enhanced UMUC3 tumor contrast even at a low imaging dose of 15 μCi/mouse.	bladder
Integrated Fourier Transform Infrared Imaging and Proteomics for Identification of a Candidate Histochemical Biomarker in Bladder Cancer.	Histopathological differentiation between severe urocystitis with reactive urothelial atypia and carcinoma in situ (CIS) can be difficult, particularly after a treatment that deliberately induces an inflammatory reaction, such as intravesical instillation of Bacillus Calmette-Guèrin. However, precise grading in bladder cancer is critical for therapeutic decision making and thus requires reliable immunohistochemical biomarkers. Herein, an exemplary potential biomarker in bladder cancer was identified by the novel approach of Fourier transform infrared imaging for label-free tissue annotation of tissue thin sections. Identified regions of interest are collected by laser microdissection to provide homogeneous samples for liquid chromatography-tandem mass spectrometry-based proteomic analysis. This approach afforded label-free spatial classification with a high accuracy and without interobserver variability, along with the molecular resolution of the proteomic analysis. Cystitis and invasive high-grade urothelial carcinoma samples were analyzed. Three candidate biomarkers were identified and verified by immunohistochemistry in a small cohort, including low-grade urothelial carcinoma samples. The best-performing candidate AHNAK2 was further evaluated in a much larger independent verification cohort that also included CIS samples. Reactive urothelial atypia and CIS were distinguishable on the basis of the expression of this newly identified and verified immunohistochemical biomarker, with a sensitivity of 97% and a specificity of 69%. AHNAK2 can differentiate between reactive urothelial atypia in the setting of an acute or chronic cystitis and nonmuscle invasive-type CIS.	bladder
Targeting Epidermal Growth Factor Receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (HER2) Expressing Bladder Cancer Using Combination Photoimmunotherapy (PIT).	"Bladder cancer (BC) is heterogeneous and expresses various cell surface targets. Photoimmunotherapy (PIT) involves monoclonal antibodies (MAbs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by near infra-red light (NIR) to specifically target tumors. We have demonstrated that tumors expressing EGFR can be targeted with PIT. However, PIT may be less effective when a tumor lacks ""overwhelming"" expression of a single target such as EGFR. We present a combinatorial PIT approach for targeting BC expressing EGFR and HER2, using PA- labeled panitumumab (pan) and trastuzumab (tra), respectively. Human BC tissues and cell lines were analyzed for EGFR and HER2 expression. Efficacy of PA-labeled MAbs singly and in combination was analyzed. About 45% of BC tissues stain for both EGFR and HER2. In vitro, the combination of pan IR700 and tra IR700 with NIR was more efficacious than either agent alone. Tumor xenografts treated with combination PIT showed significant tumor growth retardation. Combination PIT is a promising approach for treating BC with low/moderate expression of surface receptors. In addition, given the molecular heterogeneity of bladder cancer, targeting more than one surface receptor may allow for more effective cell death across different bladder tumors."	bladder
Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells.	Urinary bladder cancer (UBC) is characterized by frequent recurrence and metastasis despite the standard chemotherapy with gemcitabine and cisplatin combination. Histone modifiers are often dysregulated in cancer development, thus they can serve as an excellent drug targets for cancer therapy. Here, we investigated whether G9a, one of the histone H3 methyltransferases, was associated with UBC development. We first analyzed clinical data from public databases and found that G9a was significantly overexpressed in UBC patients. The TCGA Provisional dataset showed that the average expression level of G9a in primary UBC samples (n = 408) was 1.6-fold as much as that in normal bladder samples (n = 19; P < 0.001). Then we used small interfering RNA to knockdown G9a in human UBC T24 and J82 cell lines in vitro, and observed that the cell viability was significantly decreased and cell apoptosis induced. Next, we choosed UNC0642, a small molecule inhibitor targeting G9a, with low cytotoxicity, and excellent in vivo pharmacokinetic properties, to test its anticancer effects against UBC cells in vitro and in vivo. Treatment with UNC0642 dose-dependently decreased the viability of T24, J82, and 5637 cells with the IC(50) values of 9.85 ± 0.41, 13.15 ± 1.72, and 9.57 ± 0.37 μM, respectively. Furthermore, treatment with UNC0642 (1-20 μM) dose-dependently decreased the levels of histone H3K9me2, the downstream target of G9a, and increased apoptosis in T24 and J82 cells. In nude mice bearing J82 engrafts, administration of UNC0642 (5 mg/kg, every other day, i.p., for 6 times) exerted significant suppressive effect on tumor growth without loss of mouse body weight. Moreover, administration of UNC0642 significantly reduced Ki67 expression and increased the level of cleaved Caspase 3 and BIM protein in J82 xenografts evidenced by immunohistochemistry and western blot analysis, respectively. Taken together, our data demonstrated that G9a may be a promising therapeutic target for UBC, and an epigenetics-based therapy by UNC0642 is suggested.	bladder
Upper urinary tract recurrence following bladder cancer therapy: a review of surveillance and management.	PURPOSE OF REVIEW: Our aim is to review recent investigations into the recurrence of urothelial carcinoma in the upper urinary tract following bladder cancer therapy focusing on surveillance and management. RECENT FINDINGS: After radical cystectomy, rates of recurrence in the upper tract are between 0.75 and 6.4%. The poor prognosis of upper tract urothelial carcinoma (UTUC) is in part attributable to delayed diagnosis. Guidelines recommend a gradual de-escalation of surveillance in disease-free patients with the potential for discontinuation beyond 5 years. Previous guideline audits have shown that recurrences are still missed, suggesting a need for longer follow-up. Studies propose risk stratifying patients by age, comorbidities, and tumor stage to warrant closer surveillance and identify adjuvant therapy candidates. Larger studies are needed to advise treatment of UTUC after a urothelial bladder cancer (UBC) diagnosis, as these patients face poorer outcomes following radical nephroureterectomy. Clinical trials have demonstrated the efficacy of neoadjuvant and adjuvant systemic therapy after radical nephroureterectomy for primary UTUC; however, the literature is lacking robust data on patients who develop urothelial carcinoma in the upper tract following an initial UBC diagnosis. SUMMARY: Many asymptomatic recurrences of urothelial carcinoma in the upper tract are undetected by current surveillance guideline recommendations. Higher level evidence is needed to confirm the efficacy of prolonged and risk-adapted surveillance of patients with UBC and the extirpative management of recurrence in the upper tract after UBC treatment.	bladder
Multiple cutaneous metastasis of synchronous urothelial carcinoma of the bladder and the renal pelvis: a case report.	INTRODUCTION: Cutaneous metastatic disease arising from urinary tract carcinoma is rare and associated with a poor prognosis. We report a case of metastatic disease occurring in a patient treated for synchronous urothelial tumor of the bladder and left renal pelvis. CASE PRESENTATION: A 61-year-old Caucasian man was treated for a synchronous urothelial tumor of the bladder and left renal pelvis. He had an en bloc radical cystectomy and left ureteronehprectomy associated with a cutaneous transileal urinary diversion and lymph node dissection. He was scheduled for chemotherapy but was lost to follow-up. He consulted 1 year later with growing skin tumors that were confirmed to be metastatic disease, and he was referred to the oncology department for palliative chemotherapy. CONCLUSION: Cutaneous metastatic disease is a rare entity with poor prognosis. The main treatment remains chemotherapy; however, single-site metastasis should be considered for metastasectomy.	bladder
Cigarette smoking promotes bladder cancer via increased platelet-activating factor.	Cigarette smoking is the number one risk factor for bladder cancer development and epidemiological data suggest that nearly half of all bladder cancer patients have a history of smoking. In addition to stimulating the growth of a primary tumor, it has been shown that there is a correlation between smoking and tumor metastasis. Platelet activating factor (PAF) is expressed on the cell surface of the activated endothelium and, through binding with the PAF-receptor (PAF-R), facilitates transendothelial migration of cells in the circulation (McHowat et al. Biochemistry 40:14921-14931; 2001). In this study, we show that the exposure of bladder cancer cells to cigarette smoke extract (CSE) results in increased PAF accumulation and increased expression of the PAF-R. Furthermore, treatment with CSE increases adherence of bladder cancer cells to bladder endothelial cells and could be abrogated by pretreatment with ginkgolide B. Immunohistochemical analysis of tumor biopsy samples from bladder cancer patients who smoked revealed increased PAF and the PAF-R in tumor regions when compared to normal tissue. These data highlight a pathway in bladder cancer that is influenced by CSE which could facilitate primary tumor growth and increase metastatic potential. Targeting of the PAF-PAFR interaction could serve as a beneficial therapeutic target for managing further growth of a developing tumor.	bladder
Hypoxia-elevated circELP3 contributes to bladder cancer progression and cisplatin resistance.	Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance. Decreasing the level of circELP3 via siRNA clearly reduced the in vitro proliferation and cisplatin resistance of bladder cancer cells and promoted apoptosis. Interfering with circELP3 suppressed tumor xenograft growth in nude mice in vivo. In addition, lower circELP3-expressing bladder cancer cells displayed poorer self-renewal capacity, as demonstrated by lower levels of sphere formation and stem cell marker expression. Furthermore, in human bladder cancer patients, strong correlations between a high circELP3 level and advanced tumor grade and lymph node metastasis were observed. In summary, we provide the first direct evidence that circular RNA participates in the adaptive response to hypoxia and may play a role in the progression and drug resistance of bladder cancer.	bladder
Bladder cancer with Indian ink.	72 year old female with a historyof breast cancer in remission, under study formonosymptomatic haematuria. Cystoscopy studyshows pigmented mucosal areas...	bladder
Unusual radiologic manifestation of pseudoprogression in pulmonary metastases after durvalumab treatment in metastatic bladder urothelial cancer.	Durvalumab is an immune checkpoint inhibitor that blocks PD-L1. Unlike cytotoxic chemotherapy or molecularly targeted agents, immune checkpoint inhibitors occasionally present distinct response patterns, including radiologic pseudoprogression (initial tumor enlargement with subsequent tumor regression) and immune-related adverse events in normal tissues. We report a case of unusual computed tomography (CT) findings of pseudoprogression of pulmonary metastases in a patient with metastatic bladder cancer after durvalumab treatment: multiple pulmonary metastases turned into ground-glass opacity on first follow-up CT; on second follow-up CT, and after sustained treatment of the PD-L1 inhibitor, the lesion was resolved.	bladder
Efficacy of Split Schedule Versus Conventional Schedule Neoadjuvant Cisplatin-Based Chemotherapy for Muscle-Invasive Bladder Cancer.	Neoadjuvant cisplatin-based chemotherapy (NAC; 70 mg/m(2)) is standard of care for muscle-invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m(2) on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (<pT2) pathologic response rates between split schedule (SS) and conventional schedule (CS) pts, after 1:1 matching on chemotherapy regimen, number of cycles, tumor histology, and clinical stage. Eighty matched pts were identified. pT0 rates were 17.5% (95% confidence interval [CI], 7%-33%) and 32.5% (95% CI, 19%-49%) in SS and CS cisplatin pts, respectively (p = .21), corresponding to an odds ratio for pT0 of 0.45 (95% CI, 0.16-1.31) with SS cisplatin. Split schedule cisplatin was associated with numerically but not statistically significant lower pathologic response rates relative to full dose.	bladder
The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer.	Accumulating evidence shows that circular RNAs (circRNAs) function as microRNA sponges that regulate gene expression in the progression of human cancers. However, the roles of circRNAs and functional miRNA sponges in bladder cancer (BC) remain largely unknown. In the present study, we applied bioinformatics methods and hypothesised that miR-146b may target the 3'-untranslated region (UTR) of CARMA3 mRNA and circINTS4 may serve as a sponge for miR-146b in BC tumorigenesis. Expression of circINTS4 was significantly increased in miR-146b-downregulated BC tissues and cell lines compared to adjacent normal tissues. Furthermore, circINTS4 was found to control multiple pathological processes, including cell proliferation and migration, the cell cycle and apoptosis. Regarding the mechanism, circINTS4 directly bound to miR-146b to inhibit its activity of targeting the 3'-UTR of CARMA3 mRNA. In addition, circINTS4 could activate the NF-kB signalling pathway and suppress the P38 MAPK signalling pathway in a CARMA3-mediated manner in BC cells. In summary, the circINTS4/miR-146b/CARMA3 axis might serve as a promising therapeutic target for BC intervention.	bladder
Prothymosin-α enhances phosphatase and tensin homolog expression and binds with tripartite motif-containing protein 21 to regulate Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling in human bladder cancer.	Prothymosin-α (PTMA) is a small, acidic protein that is usually transported into the nucleus and involves many cellular and immunological functions. Previous studies demonstrated that aberrant location of PTMA expression exists in human bladder cancer, but the role of PTMA protein expression remains elusive. In this study, we created ectopic nuclear or cytoplasmic PTMA expression in human bladder cancer cells by infecting lentiviruses carrying wild type or deleted nuclear localization signal of the PTMA gene. The in vivo tumorigenesis assay showed PTMA protein with deleted nuclear localization signal promotes J82 xenograft tumor growth in mice and shortens their survival more so than the wild type. Chromatin immunoprecipitation showed that wild-type PTMA protein binds to the PTEN promoter and enhances phosphatase and tensin homolog (PTEN) expression. Through immunoblot proteomics and in vivo ubiquitination studies, PTMA protein can bind with tripartite motif-containing protein 21 (TRIM21) and block its ubiquitination. Also, TRIM21 can downregulate both forms of PTMA protein. In human bladder tumors, loss of nuclear PTMA expression was an unfavorable prognostic indicator for shorter disease-free survival (hazard ratio, 1.54; P = 0.009). Our data support that nuclear PTMA protein serves as a tumor suppressor in bladder cancer through upregulating PTEN and orchestrating TRIM21 for the regulation of Nrf2 signaling.	bladder
Multiregion human bladder cancer sequencing reveals tumour evolution, bladder cancer phenotypes and implications for targeted therapy.	We present an evolutionary analysis of the relative time of genetic events underlying tumorigenesis in human bladder cancers from 10 whole cystectomy specimens using multiregional whole-exome sequencing. We timed bladder cancer drivers, mutational signatures, ploidy and copy number alterations, provided evidence for kataegis and correlated alterations with tumour areas and histological phenotypes. We found that: (1) heterogeneous tumour areas/phenotypes had distinct driver mutations, (2) papillary-invasive tumours divided early into two parallel evolving branches and (3) parallel evolution of subclonal driver mutations occurred. APOBEC mutational signatures were found to be very early events, active in carcinoma in situ, and often remained a dominant source of mutations throughout tumour evolution. Genetic progression from carcinoma in situ followed driver mutations in NA13/FAT1, ZBTB7B or EP300/USP28/KMT2D. Our results point towards a more diverse mutational trajectory of bladder tumorigenesis and underpin the importance of timing of mutational processes and clonal architecture in bladder cancer as important aspects for successful prognostication and therapy. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	bladder
Induction Chemotherapy Followed by Surgery Versus Upfront Radical Cystectomy in Patients With Clinically Node-positive Muscle-invasive Bladder Cancer.	BACKGROUND: The aim of this study was to compare survival outcomes in patients with clinically node-positive muscle-invasive bladder cancer receiving induction chemotherapy (IC) followed by surgery and those who underwent upfront radical cystectomy (RC). PATIENTS AND METHODS: Outcomes were reviewed in patients with cT2-4N1-3M0 bladder cancer treated with IC followed by surgery or upfront RC between January 1995 and June 2017. Survival outcomes were analyzed using a propensity score matched cohort analysis. RESULTS: Of the 340 eligible patients, 106 received IC and 234 underwent upfront RC. The overall 3-year metastasis-free survival rate and 5-year cancer-specific survival rate of patients in the IC and RC groups were similar (49.4% vs. 46.0% and 49.6% vs. 49.8%, respectively). The 5-year cancer-specific survival rate of cN1-2 patients was higher in the IC group than the RC group (68.1% vs. 52.9%; P = .035). However, the 5-year cancer-specific survival rate of patients with cN3 cancers was significantly lower in the IC group than the RC group (19.2% vs. 44.5%; P = .015). CONCLUSIONS: In this study, IC was seen to improve cancer-specific survival in patients with cN1-2 muscle-invasive bladder cancers but was associated with poorer survival outcomes than upfront RC in patients with cN3 cancers. Further investigation in prospective, randomized studies is warranted.	bladder